Deep Brain Stimulation Therapy Research Articles

The Effects of Deep Brain Stimulation on Motor Unit Activities in Parkinson's Disease based on High-Density Surface EMG Analysis.

Tremor in Parkinson's disease (PD) is caused by synchronized activation bursts in limb muscles. Deep Brain Stimulation (DBS) is an effective clinical therapy for inhibiting tremor and improving movement disorders in PD patients. However, the neural mechanism of how tremor symptom is suppressed by DBS at motor unit (MU) level remains unclear. This paper developed a data acquisition platform for collecting physiological data in PD patients. Both high-density surface Electromyography (HD-sEMG) and kinematics data were collected concurrently before and after DBS surgery. The MU behaviors were obtained via HD-sEMG decomposition algorithm to reveal the effect of DBS on PD tremor. A data set of one tremor dominant PD patient acquired in pre-operation and post-operation (DBS-on) phases was analyzed. Preliminary results showed significant changes in MU firing rate and MU synchronization. The analysis approach introduced in this paper provides a novel perspective for studying the neural mechanism of DBS as revealed by MU activities. Clinical Relevance- This study presented an approach to investigate the effect of DBS therapy on improving tremor disorder of PD patients.

A comparison of an implanted accelerometer with a wearable accelerometer for closed-loop DBS.

Sensing technology, as well as cloud communication, is enabling the development of closed-loop deep brain stimulation (DBS) for Parkinson's disease. The accelerometer is a practical sensor that can provide information about the disease/health state of the patient as well as physical activity levels, all of which in the long-term can provide feedback information to an adaptive closed-loop control algorithm for more effective and personalized DBS therapy. In this paper, we present for the first time, acceleration streamed from Medtronic's RC+S device in patients with Parkinson's disease while at home, and compare it to accel-eration acquired concurrently from the patient's Apple Watch. We examined correlation between the accelerometer signals at varying time scales. We also compared the spectral band power obtained from the two accelerometers. While there was an average correlation of 0.37 for subject 1 and 0.50 for subject 2 between the two acceleration signals on a time scale of 10 minutes, the correlation was lower for shorter time scales on the order of seconds. There was greater spectral power in the Parkinsonian tremor band of 4-7 Hz for the externally worn accelerometer than the internal accelerometer, but the internal accelerometer showed greater relative power distributed in the higher frequencies (7-30 Hz). Thus, based on this preliminary analysis, we expect that the internal accelerometer may be used to assess patient activity and state for closed loop DBS but tremor detection may require more sophisticated signal processing. Furthermore, the internal accelerometer may contain information in higher frequency bands that reveal information about the patient state. Clinical relevance - Closed-loop DBS is expected to improve patient outcomes for the tens of thousands of Parkinson's disease patients using DBS [1], [2]. Eliminating an additional external device in order to implement closed-loop adaptive deep brain stimulation would benefit DBS patients however an understanding of what information is lost by doing so is needed to justify the ultimate design of closed-loop DBS.

Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease.

The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively. Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

Quantifying Viscous Damping and Stiffness in Parkinsonism Using Data-Driven Model Estimation and Admittance Control.

Rigidity of upper and lower limbs in Parkinson's disease (PD) is typically assessed via a clinical rating scale that is subject to human perception biases. Methodologies to quantify changes in rigidity associated with the angular position (stiffness) or velocity (viscous damping) are needed to enhance our understanding of PD pathophysiology and objectively assess therapies. In this proof of concept study, we developed a robotic system and a model-based approach to estimate viscous damping and stiffness of the elbow. Our methodology enables the subject to freely rotate the elbow using an admittance controller while torque perturbations tailored to identify the arm dynamics are delivered. The viscosity and stiffness are calculated based on the experimental data using least-squares estimation. We validated our technique using computer simulations and experiments with a nonhuman animal model of PD in the presence and absence of deep brain stimulation therapy. Our data show that stiffness and viscosity measurements can better differentiate rigidity changes than scores previously used for research, including the work and impulse scores, and the modified unified Parkinson's disease rating scale. Our estimation method is suitable for quantifying the effect of therapies on viscous damping and stiffness and studying the pathophysiological mechanisms underlying rigidity in PD.

Deep brain stimulation rectifies the noisy cortex and irresponsive subthalamus to improve parkinsonian locomotor activities

The success of deep brain stimulation (DBS) therapy indicates that Parkinson’s disease is a brain rhythm disorder. However, the manifestations of the erroneous rhythms corrected by DBS remain to be established. We found that augmentation of α rhythms and α coherence between the motor cortex (MC) and the subthalamic nucleus (STN) is characteristically prokinetic and is decreased in parkinsonian rats. In multi-unit recordings, movement is normally associated with increased changes in spatiotemporal activities rather than overall spike rates in MC. In parkinsonian rats, MC shows higher spike rates at rest but less spatiotemporal activity changes upon movement, and STN burst discharges are more prevalent, longer lasting, and less responsive to MC inputs. DBS at STN rectifies the foregoing pathological MC-STN oscillations and consequently locomotor deficits, yet overstimulation may cause behavioral restlessness. These results indicate that delicate electrophysiological considerations at both cortical and subcortical levels should be exercised for optimal DBS therapy.

Dystonic motor and phonic tics in Tourette syndrome.

Dystonic tics differ from clonic tics by their slower and more sustained nature. Dystonic tics are often present in patients with Tourette syndrome (TS) and other tic-disorders. However, their phenomenology and impact on overall impairment have not been extensively studied. We assessed clinical history and tic duration in video-recordings from patients with TS evaluated at our movement disorders clinic. Dystonic tics were defined as those lasting ≥ 1000ms (ms). Of the total of 201 patients with TS, there were 156 with video-recordings suitable for tic duration analysis, of their tics, 57 (36.5%) of whom had dystonic motor tics, including 9 (5.7%) with dystonic phonic tics. Dystonic motor tics had a duration range between 1033 and 15,000ms and dystonic phonic tics between 1132 and 17,766ms. Patients with dystonic tics were older 24.4 vs. 16.5years (P = 0.005) and had an older age at onset 12.9 vs. 7.2years (P < 0.001), than patients without dystonic tics. The bivariate analysis showed an association between the presence of dystonic tics, greater tic severity and wider body distribution. The multivariate regression analysis showed a statistical association with older age at evaluation (P = 0.001), greater tic severity on video-recordings (P = 0.001) and co-occurrence with complex motor tics (P = 0.020). The presence of dystonic tics increased the risk for being considered for deep brain stimulation therapy, odds ratio: 15.7 (P = 0.002). Dystonic tics, observed in about a third of patients with TS, are associated with increased severity of TS.

Bilateral subthalamic nucleus deep brain stimulation for refractory isolated cervical dystonia

Subthalamic nucleus (STN) deep brain stimulation (DBS) has been proven to be an alternative target choice for refractory isolated cervical dystonia (CD). However, assessments of its short and long-term safety, efficacy, and sustained effectiveness have been limited to few reports. Here, we evaluated nine consecutive refractory isolated CD patients who underwent bilateral STN DBS and accepted to short and long-term follow-up in this retrospective study. Seven time points were used to see the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores (pre-operation [baseline], 1, 3, 6, 12, 24 months post-operation and last follow-up) to assess improvement of dystonic symptoms. The 36-item Short-Form General Health Survey (SF-36) scores obtained at pre-operation and last follow-up to assess the changes in quality of life. All patients tolerated surgery well and acquired observable clinical benefits from STN DBS therapy. All patients achieved a considerable improvement in quality of life at the last follow-up. The hardware-related adverse events can be tolerated and the stimulation-related adverse events can be ameliorated by programming. Our data support the idea that bilateral STN DBS is a safety and effective method for the treatment of refractory isolated CD, with persistent and remarkable improvement in both movement and quality of life.

P 47 The Impact of directional deep brain stimulation on subthalamic beta power in Parkinson's disease

Introduction : Beta power in subthalamic local field potentials (LFPs) is a well established biomarker for bradykinesia-rigidity in idiopathic Parkinson's Disease (IPS) and is a promising feedback signal for adaptive deep brain stimulation (DBS). However, the effect of directional stimulation on this biomarker has not yet been elaborated. With new DBS-systems allowing to combine directional stimulation with relatively artifact-free recordings of local field potentials (LFPs), we want to assess the impact of directionality on beta power and motor performance. Patients & Methods : So far, 6 IPS patients implanted with Medtronic SenSight directional electrodes in the subthalamic nucleus (STN) have been included in the study. LFPs were recorded post-operatively and during a 3 months follow up visit (3MFU) with the patient at rest using the Medtronic Percept PC implantable pulse-generator. Additionally, at the 3MFU, a monopolar review of all segmented contacts (separately and combined as ring) was carried out in the medication “off” state. A rotameter task was used to assess motor performance. Following each block consisting of 2 minutes of rest and 30 seconds of rotation, stimulation amplitude was increased stepwise up to a maximum amplitude of 3 mA or the occurrence of side effects. LFPs were streamed throughout the review. The primary outcome is the reduction of mean beta power with directional stimulation compared with (1) no stimulation and (2) ring stimulation. The secondary outcomes are: (1) Beta burst length distribution, (2) motor performance and (3) rate of side effects with directional compared to ring stimulation. Results : Further patient inclusion to a minimum of 10 patients is planned before the summit. Directional and ring stimulation led to dose-dependent reduction of mean beta power in the STN. Stimulation had an effect on both movement amplitude and velocity. In 4 out of 6 patients, the side effect threshold was higher with directional stimulation compared to ring stimulation. At the summit, we will also report changes in beta burst length distribution with directional compared to ring stimulation and the predictive value of beta power in postoperative intersegmental rest recordings for the clinically most effective directional contact. Conclusion : Our study contributes to characterizing LFP beta power in the context of directional stimulation and its relation to motor performance. This is a prerequisite for combining directional stimulation with beta-driven adaptive DBS, which ultimately could further improve DBS therapy.

P 43 Optimizing beta-burst driven adaptive deep brain stimulation for Parkinson's disease

Introduction Adaptive deep brain stimulation (DBS) aims at improving DBS therapy by adjusting stimulation amplitude to patient specific biomarkers tracked in real-time. In Parkinson’s disease (PD), a promising closed-loop approach exploits fast fluctuations of beta power (beta bursts) in subthalamic local field potentials (LFP). With this method, stimulation is applied as soon as beta bursts of a given magnitude and duration are detected. However, closed-loop algorithms offer clinicians a wide range of possible settings. This will further increase the parameter space and thus the complexity of DBS programming, ultimately limiting ease of clinical usability. To increase the translational potential of adaptive DBS, this constraint must be overcome by narrowing down the parameter space towards a clinically optimal combination of stimulation settings. Objectives To explore the parameter space of a beta burst driven adaptive DBS algorithm and to characterize its neurophysiological and behavioral correlates in order to identify a clinically optimal parameter combination. Patients & methods A research platform for adaptive stimulation has been designed comprising a stimulation artifact suppressing amplifier, a custom-made software interface and an external neurostimulator. On this platform, a configurable LFP beta burst driven closed-loop algorithm has been implemented. This setup was used to conduct closed-loop stimulation in PD patients undergoing two-stage-surgery for DBS. Rest recordings were combined with a standardized motor task to quantify stimulation-induced behavioral effects. By systematically changing the minimum beta burst duration upon which stimulation is triggered and the amount of smoothing applied to real-time beta power, the parameter space of this algorithm was explored. Results Stimulation patterns were governed by parameter combination with higher minimum burst duration leading to less frequent stimulation. Beta dynamics varied depending on parameter choice. Clinically optimal settings are yet to be explored. Conclusion The choice of adaptive DBS parameter combination strongly influences stimulation patterns and stimulation-induced neurophysiological responses. Combined recordings of neurophysiological and behavioral adaptive DBS correlates for different parameter combinations may pave the way for guiding parameter choice based on electrophysiological evaluation. This may facilitate the clinical translation of adaptive DBS.

Initial Clinical Outcome With Bilateral, Dual-Target Deep Brain Stimulation Trial in Parkinson Disease Using Summit RC + S.

Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson disease (PD). Although both subthalamic nucleus (STN) and globus pallidus (GP) DBS show equivalent efficacy in PD, combined stimulation may demonstrate synergism. To evaluate the clinical benefit of stimulating a combination of STN and GP DBS leads and to demonstrate biomarker discovery for adaptive DBS therapy in an observational study. We performed a pilot trial (n = 3) of implanting bilateral STN and GP DBS leads, connected to a bidirectional implantable pulse generator (Medtronic Summit RC + S; NCT03815656, IDE No. G180280). Initial 1-year outcome in 3 patients included Unified PD Rating Scale on and off medications, medication dosage, Hauser diary, and recorded beta frequency spectral power. Combined DBS improved PD symptom control, allowing >80% levodopa medication reduction. There was a greater decrease in off-medication motor Unified PD Rating Scale with multiple electrodes activated (mean difference from off stimulation off medications -18.2, range -25.5 to -12.5) than either STN (-12.8, range -20.5 to 0) or GP alone (-9, range -11.5 to -4.5). Combined DBS resulted in a greater reduction of beta oscillations in STN in 5/6 hemispheres than either site alone. Adverse events occurred in 2 patients, including a small cortical hemorrhage and seizure at 24 hours postoperatively, which resolved spontaneously, and extension wire scarring requiring revision at 2 months postoperatively. Patients with PD preferred combined DBS stimulation in this preliminary cohort. Future studies will address efficacy of adaptive DBS as we further define biomarkers and control policy.

Case series investigating the differences between stimulation of rostral zona incerta region in isolation or in conjunction with the subthalamic nucleus on acute clinical effects for Parkinson’s disease

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) is a highly effective therapy for movement disorders including Parkinson’s disease (PD). One focus of research has been to explore whether stimulation of the rostral zona incerta (rZI) region contributes to the efficacy observed in STN DBS therapy. ObjectiveIn this study, we conducted a case series to evaluate the clinical efficacy and adverse effects of stimulation to the rZI region in isolation and in conjunction with STN stimulation. MethodsVolunteers with PD (N = 5), treated with STN DBS, and determined to have a dorsal contact within the region of rZI were recruited to participate. Following evaluation of tolerability, each volunteer underwent routine motor assessments during three stimulation parameter conditions: STN, rZI, and co-stimulation STN + rZI. Both participant and clinical examiner were blinded to the condition. Efficacy was measured with the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). Volumes of tissue activation for all conditions were assessed for STN and rZI coverage. ResultsNo significant differences between measures of MDS-UPDRS and UDysRS were observed for the three stimulation settings. Although not statistically significant, results showed that 2 participants preferred STN + rZI co– stimulation, 2 participants preferred STN stimulation, and 1 participant preferred rZI stimulation and 4/5 participant preferences were consistent with clinician preference. ConclusionsFindings from this case series support further investigation into co-stimulation of the rZI region and STN for PD motor symptoms.

Essential Tremor-Do We Have Better Therapeutics? A Review of Recent Advances and Future Directions.

Essential tremor (ET) is a very common condition that significantly impacts quality of life. Current medical treatments are quite limited, and while surgical treatments like deep brain stimulation (DBS) can be very effective, they come with their own limitations as well as procedural risks. This article reviews updates on recent advances and future directions in the treatment of ET. A new generation of pharmacologic agents specifically designed for ET is in clinical trials. Advances in DBS technology continue to improve this therapy. MRI-guided focused ultrasound (MRgFUS) is now an approved noninvasive ablative treatment for ET that is effective and shows potential for continuing improvement. The first peripheral stimulation device for ET has also now been approved. This article reviews updates on the treatment of ET, encompassing pharmacologic agents in clinical trials, DBS, MRgFUS, and noninvasive stimulation therapies. Recent treatment advances and future directions of development show a great deal of promise for ET therapeutics.

429 Racial Disparities Persist Despite Increased Utilization of Deep Brain Stimulation Surgery for Parkinson’s Disease

INTRODUCTION: Deep brain stimulation (DBS) provides improved quality of life for properly selected individuals with Parkinson’s disease (PD). Though DBS is a widely accepted and efficacious therapy for PD, significant racial disparities have been reported in the access to DBS, particularly for Black patients. METHODS: The National Inpatient Sample (NIS) was queried to identify PD patients who underwent DBS placement between 2002 and 2018. We examined DBS utilization relative to PD admissions, patient characteristics over time, and whether ACA passage was associated with changes in insurance and DBS utilization among different racial/ethnic groups. RESULTS: In 2014-2018, the odds of PD patients receiving DBS therapy increased 56% compared to 2002-2005 (p &lt; 0.001). In a multivariate logistic regression analysis, the most important factors affecting the likelihood of DBS surgery were race, insurance status and the presence of comorbidities. Black PD patients were 1/5 as likely as White patients to undergo DBS placement (p &lt; 0.001). Individuals with = 2 comorbidities were 20 times less likely to undergo DBS. Patients insured privately compared to those insured by Medicare/Medicaid were 5.22 times as likely to undergo DBS. Passage of the ACA was associated with 2.62 times higher odds of DBS in 2010-2013 for Black PD patients compared to 2002-2005 (p = 0.008). During the period 2014-2018, Black PD patients were 2.33 times more likely to undergo DBS compared to the period 2002-2005 (p = 0.008). CONCLUSION: DBS is increasingly used for healthy, privately insured PD patients. Significant racial disparities persist in the use of DBS for PD despite a modest improvement following passage of the ACA, but prior to most of its implementation, indicating other factors contributed to this change.

Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson’s disease focusing on correlations with motor symptoms

The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson’s disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson’s disease sleep scale (PDSS-2), and Beck depression inventory (BDI). Our results showed significantly decreased PACAP levels in PD patients without deep brain stimulation (DBS) therapy and in akinetic-rigid subtype; additionally we also observed a further decrease in the HY stage 3 and 4. Elevated PACAP levels were found in patients with DBS. There were no significant correlations between PACAP level with MDS-UPDRS, type of pharmacological treatment, PDSS-2 sleepiness, or depression (BDI) scales, but we found increased PACAP level in patients with more severe sleepiness problems based on the ESS scale. Based on these results, we suggest that following the alterations of PACAP with other frequently used clinical biomarkers in PD patients might improve strategic planning of further therapeutic interventions and help to provide a clearer prognosis regarding the future perspective of the disease.

Necessity and feasibility of remote tele-programming of deep brain stimulation systems in Parkinson's disease

IntroductionOutcomes after deep brain stimulation (DBS) therapy are dependent on good surgical placement in the target nucleus and optimized stimulation parameters through multiple programming sessions. This often requires frequent travel to a specialized DBS center, which presents a challenge for those with limited access. Recently, the FDA approved a remote tele-programming solution for DBS. To determine if remote tele-programming of DBS systems is beneficial and useful for Parkinson's Disease (PD) patients, Parkinson's Foundation hosted a survey in collaboration with Abbott Labs. MethodsThe survey was conducted to assess the need for telemedicine among PD patients with DBS and the usability of the telehealth interface for DBS teleprogramming. The survey included two validated instruments: The Effective Accessibility and Accommodation survey (EAA) and the Telehealth Usability Questionnaire (TUQ). Results47 patients completed the EAA and 41 completed the TUQ. Results from the EAA revealed more than a third of PD patients cannot easily get to a clinic for various reasons, and more than a quarter reported difficulty contacting their clinic for advice. Results from the TUQ revealed overall satisfaction with the DBS remote programming telehealth interface and care provided. The majority of respondents reported that remote tele-programming visits are similar in quality to in-person visits. ConclusionThis study provides support for the use of telehealth and tele-programming for DBS management in PD patients. The ability to use remote technologies for care will increase access to DBS and mitigate the disparities that currently prevent access to care.

The Fast Gray Matter Acquisition T1 Inversion Recovery Sequence in Deep Brain Stimulation: Introducing the Rubral Wing for Dentato-Rubro-Thalamic Tract Depiction and Tremor Control

BackgroundThe dentato-rubro-thalamic tract (DRT) is currently considered as a potential target in deep brain stimulation (DBS) for various types of tremor. However, tractography depiction can vary depending on the included brain regions. The fast gray matter acquisition T1 inversion recovery (FGATIR) sequence, with excellent delineation of gray and white matter, possibly provides anatomical identification of rubro-thalamic DRT fibers. ObjectiveThis study aimed to evaluate the FGATIR sequence by comparison with DRT depiction, electrode localization, and effectiveness of DBS therapy. Materials and MethodsIn patients with DBS therapy because of medication-refractory tremor, the FGATIR sequence was evaluated for depiction of the thalamus, red nucleus (RN), and rubro-thalamic connections. Deterministic tractography of the DRT, electrode localization, and tremor control were compared. The essential tremor rating scale was used to assess (hand) tremor. Tremor control was considered successful when complete tremor suppression (grade 0) or almost complete suppression (grade 1) was observed. ResultsIn the postoperative phase, we evaluated 14 patients who underwent DRT-guided DBS: 12 patients with essential tremor, one with tremor-dominant Parkinson disease, and one with multiple sclerosis, representing 24 trajectories. Mean follow-up was 11.3 months (range 6–19 months). The FGATIR sequence provided a clear delineation of a hypointense white matter tract within the hyperintense thalamus. In coronal plane, this tract was most readily recognizable as a “rubral wing,” with the round RN as base and lateral triangular convergence. The deterministic DRT depiction was consistently situated within the rubral wing. The number of active contacts located within the DRT (and rubral wing) was 22 (92%), of which 16 (73%) showed successful tremor control. ConclusionsThe FGATIR sequence offers visualization of the rubro-thalamic connections that form the DRT, most readily recognizable as a “rubral wing” in coronal plane. This sequence contributes to tractographic depiction of DRT and provides a direct anatomical DBS target area for tremor control.

Periodic Artifact Removal With Applications to Deep Brain Stimulation

Deep brain stimulation (DBS) therapies have shown clinical success in the treatment of a number of neurological illnesses, including obsessive-compulsive disorder, epilepsy, and Parkinson’s disease. An emerging strategy for increasing the efficacy of DBS therapies is to develop closed-loop, adaptive DBS systems that can sense biomarkers associated with particular symptoms and in response, adjust DBS parameters in real-time. The development of such systems requires extensive analysis of the underlying neural signals while DBS is on, so that candidate biomarkers can be identified and the effects of varying the DBS parameters can be better understood. However, DBS creates high amplitude, high frequency stimulation artifacts that prevent the underlying neural signals and thus the biological mechanisms underlying DBS from being analyzed. Additionally, DBS devices often require low sampling rates, which alias the artifact frequency, and rely on wireless data transmission methods that can create signal recordings with missing data of unknown length. Thus, traditional artifact removal methods cannot be applied to this setting. We present a novel periodic artifact removal algorithm for DBS applications that can accurately remove stimulation artifacts in the presence of missing data and in some cases where the stimulation frequency exceeds the Nyquist frequency. The numerical examples suggest that, if implemented on dedicated hardware, this algorithm has the potential to be used in embedded closed-loop DBS therapies to remove DBS stimulation artifacts and hence, to aid in the discovery of candidate biomarkers in real-time. Code for our proposed algorithm is publicly available on Github.

Characterizing the trends in patient demographics, complications, and short-term outcomes after deep brain stimulation procedures

BackgroundIndications for deep brain stimulation (DBS) are rapidly growing within functional neurosurgery. The objective of this study was to characterize national trends in demographics and complications across distinct populations of DBS patients. MethodsWe identified patients from the 2008–2018 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data File (PUF) who underwent an implantation or revision procedure for DBS. Summary statistics for postoperative infection rate, noninfectious complication rate, total hospital length of stay, discharge disposition, mortality, reoperation or readmission, and time from operation to readmission were obtained. Patients were categorized by diagnosis for DBS treatment. Outcomes for each diagnosis group were compared to outcomes for the total study population. ResultsDBS patients who underwent primary implantation procedures had low rates of postoperative infections (1.2%), noninfectious complications (0.8%), and mortality (0.1%) and a high likelihood of discharge home (97.6%). In addition, a large percentage of patients presented for revision or removal of neurostimulators (34.2% of cases) or treatment of long-term hardware infection (4.5%). Compared with patients with other diagnoses, patients with Parkinson disease experienced lower rates of noninfectious complications (odds ratio 0.32; 95% CI, 0.15–0.63; p = 0.002) and fewer unplanned reoperations (odds ratio 0.60; 95% CI, 0.39–0.92; p = 0.02). ConclusionAnalysis of a national database suggests that DBS is a relatively safe treatment across several different patient populations. These overall favorable results support the continued practice of DBS surgery and provide encouraging validation for increasing access to DBS therapy for new indications that are being actively investigated.

Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in obsessive-compulsive disorder.

Detection of neural signatures related to pathological behavioral states could enable adaptive deep brain stimulation (DBS), a potential strategy for improving efficacy of DBS for neurological and psychiatric disorders. This approach requires identifying neural biomarkers of relevant behavioral states, a task best performed in ecologically valid environments. Here, in human participants with obsessive-compulsive disorder (OCD) implanted with recording-capable DBS devices, we synchronized chronic ventral striatum local field potentials with relevant, disease-specific behaviors. We captured over 1,000 h of local field potentials in the clinic and at home during unstructured activity, as well as during DBS and exposure therapy. The wide range of symptom severity over which the data were captured allowed us to identify candidate neural biomarkers of OCD symptom intensity. This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders.

Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson's Disease.

Sleep disorders are one of the most common non-motor symptoms in Parkinson's disease (PD). It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. The most cited sleep disorders in PD included insomnia, restless legs syndrome (RLS), rapid eye movement (REM), sleep behavior disorders (RBD), excessive daytime sleepiness (EDS) and sleep disordered breathing (SDB), which can appear alone or several at the same time. In this review, we listed the recommended pharmacological treatments for common sleep disorders in PD, and discussed the recommended dosages, benefits and side effects of relative drugs. We also discussed non-pharmacological treatments to improve sleep quality, including sleep hygiene education, exercise, deep brain stimulation, cognitive behavior therapy and complementary therapies. We tried to find proper interventions for different types of sleep disorders in PD, while minimizing relative side effects.